B cell proliferation and B cell differentiation have been recognized as distinct components of the humoral immune response. Factors that regulate the immune response may do so by interacting with one or the other of these two B cell functions. Extending our investigation of the regulation of immune response, we propose to characterize the mechanism of action of immunomodulators - LPS, macrophages, supressor cells - in these terms. Specifically, we propose to (1) dissect mechanisms of LPS-induced B cell proliferation and differentiation, (2) define effects of LPS on the T cell-dependent production of antibody to SRBC in terms of their relation to proliferation and differentiation of B cells, (3) determine the role of proliferation signals and differentiation signals in the T cell-independent production of antibody, and (4) characterize suppressor cells in terms of their effects on proliferation and differentiation of B cells. We have developed methods and reagents that provide the basis for incisive analysis, and we have established their usefulness in the initial phase of this investigation. One example is tumor necrosis serum (induced by LPS) which has become an effective tool in this investigation of B cell differentiation. The proposed program is part of the efforts of our group directed at developing more effective approaches to cancer immunotherapy by clarifying basic aspects of immunoregulation.